Stratum comeum

Sodium dodecyl sulfate has been used to induce a dry, scaly skin condition in human subjects by daily treatment with a 4% aqueous solution on one leg over a period of 2 weeks. Measurements were made of stratum comeum hydration, scaliness, and lipid composition which were used to assess in vivo surfactant perturbations on desquamation [381]. 

Cholesterol is found in many biological membrane and is the main sterol of animal organisms. It is eqnimolar with phospholipids in membranes of liver cell, erythrocytes, and myelin, whereas in human stratum comeum it lies in the outermost layer of the epidermis... 

A study using skin samples from healthy humans revealed that trichloroethylene extracts lipids from the stratum comeum (Goldsmith et al. 1988). The study indicates that lipid extraction is the reason for whitened skin following exposure to solvents such as trichloroethylene. 

Rapid dermal absorption of trichloroethylene is evident from a study in which peak blood and exhaled air concentrations occurred within 5 minutes after a human subject immersed one hand in a solution of unspecified trichloroethylene concentration for 30 minutes (Sato and Nakajima 1978). Studies on dermal absorption of trichloroethylene in humans, as well as animals, are complicated by the fact that exposure in these studies is usually by direct contact of the skin with the undiluted chemical. Trichloroethylene is a lipophilic solvent that defats the skin and disrupts the stratum comeum, thereby enhancing its own absorption. Thus, the rate of absorption probably increases in a nonlinear fashion with greater epidermal disruption. Although the extent of absorption through the skin may be relatively modest with normal industrial use (Sato and Nakajima 1978 Stewart and Dodd 1964), there is insufficient information to evaluate the effects of chronic, low-level exposure in hiunans, especially when multiple routes may be involved. 

Goldsmith LB, Friberg SE, Wahlberg JE. 1988. The effect of solvent extraction on the lipids of the stratum comeum in relation to observed immediate whitening of the skin. Contact Dermatitis 19 348-350. 

Raith and Neubert [57] have developed a method for the profihng of human stratum comeum ceramides. The method enables the investigation of the role of ceramides in maintaining the barrier function of stratum comeum. TLC using automated multiple development was modified for semipreparative purposes. The fractionation of complex lipid extracts using this method ensured specific, sensitive, and... 

Human skin is the largest organ in the human body. It is fundamentally important to health as the semi-permeable barrier - the first line of defence - between the body and the external world. However, it remains relatively inaccessible to conventional magnetic resonance imaging, firstly because it is thin and therefore requires high spatial resolution, and secondly because it is characterized by relatively short T2 relaxation times, particularly in the outermost stratum comeum. Conventional studies have not usually achieved a resolution better than 70-150 pm, with an echo time of the order of a millisecond or so. As a planar sample, skin has proved amenable to GARField study where it has been possible to use both a shorter echo time and achieve a better spatial resolution, albeit in one direction only. Such studies have attracted the interest of the pharmaceutical and cosmetic industries that are interested in skin hydration and the transport of creams and lotions across the skin. 

Fig. 2.3.8 Lower GARField profiles of a human skin sample sandwiched between two glass slides, recorded immediately after the sample was floated onto the first slide and again approximately 90 min later. Upper increasing the pulse gap T from 150 to 500 ps increases mobility contrast and allows discrimination between the stratum comeum (right) and viable epidermis (left). Again two profiles are shown, recorded approximately 90 min apart.

Skin functions as both, an important physical barrier to the absorption of toxic substances and simultaneously as a portal of entry of such substances. The stratum comeum of the epidermis is most significant in providing some degree of physical... 

Emollients Moisturize stratum comeum, restore barrier... 

Hirsutism Ichthyosis Abnormal, heavy hairiness A disease characterized by dryness, roughness, and scaliness of the skin caused by hypertrophy of the stratum comeum... 

Ghosh [548] used cellulose nitrate microporous filters (500 pm thick) as scaffold material to deposit octanol into the pores and then under controlled pressure conditions, displace some of the oil in the pores with water, creating a membrane with parallel oil and water pathways. This was thought to serve as a possible model for some of the properties of the outermost layer of skin, the stratum comeum. The relative proportions of the two types of channel could be controlled, and the properties of 5-10% water pore content were studied. Ibuprofen (lipophilic) and antipyr-ine (hydrophilic) were model drugs used. When the filter was filled entirely with water, the measured permeability of antipyrine was 69 (in 10 6 cm/s) when 90% of the pores were filled with octanol, the permeability decreased to 33 95% octanol content further decreased permeability to 23, and fully octanol-filled filters indicated 0.9 as the permeability. 

Anderson, B. D. and Raykar, P. V., Solute structure-permeability relationships in human stratum comeum, J. Invest. Derm., 1989, 93, 280-286. 

The pH of intact skin ranges from about 4.8 to 6.0, while interstitial fluid exhibits a pH that is near neutral. The low pH on skin is attributed mainly to the presence of the so-called acid mantle , a natural skin barrier to the external environment [172], Wagner et al. [173] measured both in-vivo and in-vitro pH profiles across human stratum comeum (SC) using the tape stripping technique and a flat surface pH electrode (InLab 426 from Mettler Toledo). They found a steep pH increase from pH 6 to 8 in the first 100 pm after the removal of the SC. 

TEWL), a measure of damage to the stratum comeum, also increased after exposure to JP-8 [34,35,38,39]. 

Urocanic acid (2-propanoic acid 3-[lH-imidazol-4-yl] is located superficially in the stratum comeum. Metabolism of epidermal UCA does not occur in situ due to the absence of urocanase, resulting in the accumulation of UCA in the epidermis. Upon UV exposure, naturally occurring trans-UCA converts to the d.s-isomer, in a dose dependent manner, until the photostationary state is reached, when equal quantities of trans- and m-UCA are found in the skin.15 Based on an analysis of the action spectrum for UV-induced immune suppression, and the fact that no immune suppression was observed in mice whose stratum comeum was previously removed by tape stripping, De Fabo and Noonan suggested that urocanic acid was the photoreceptor for UV-induced immune suppression.16 Since the initial experiments many others have documented, the ability of ris-UCA to initiate immune suppression, documented its presence in the serum of UV-irradiated mice, and demonstrated that m-UCA plays a role in UV-induced skin cancer induction. (For a more complete review of the role of m-UCA in immune suppression see two excellent reviews by Norval and colleagues.1718)... 

Strid, J., Hourihane, J., Kimber, I., Callard, R. and Strobel, S., Disruption of the stratum comeum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response. Fur. J. Immunol., 34, 2100, 2004. 

A. In general, any factor that increases absorption through the stratum comeum or mucous membrane will also increase the severity of an intrinsic response. Unless this factor mirrors potential exposure conditions, it may, in turn, adversely affect the relevance of test results. 

The chemical incorporated in a vehicle should reach the surface of the skin at a suitable rate and concentration. If the site of action lies in the deeper layers of the epidermis or below, the substance must cross the stratum comeum, if the skin is intact. Both processes, diffusion from the dosage form and diffusion through the skin barriers, are inextricably linked. They should be considered simultaneously and can be influenced by the choice of formulation. 

The physical state of the skin is considerable affected by external factors such as relative humidity, temperature, and air movement at the skin surface. If this contact is broken (for example, by external applications of ointments or creams), it is reasonable to assume that the new skin will change in some way, sometimes to an extent that creates new conditions of permeability for the test material. This would be the case, for example, if the stratum comeum becomes more hydrated than normal due to the topical delivery form. Temperature might also have an effect, as is the case when any constituents of the vehicle affect the inner structure of the skin through interactions with endogenous skin substances. Often several of these processes occur together. 

The homy layer consists of about 10% extracellular components such as lipids, proteins, and mucopolysaccharides. Around 5% of the protein and lipids form the cell wall. The majority of the remainder is present in the highly organized cell contents, predominantly as keratin fibers, which are generally assigned an a-helical structure. They are embedded in a sulphur-rich amorphous matrix, enclosed by lipids that probably he perpendicular to the protein axis. Since the stratum comeum is able to take up considerably more water than the amount that corresponds to its volume, it is assumed that this absorbed fluid volume is mainly located in the region of these keratin structures. 

FIGURE 13.3. Sorption isotherms of water vapor as a function of the relative humidity, composition of constituents, and water content in the stratum comeum. 

If the substances have passed the stratum comeum, they also generally diffuse into the living part of the epidermis, reach the circulation, and then have systemic effects depending on the amount absorbed. Because these are often constituents of formulations, one generally expects them to have little direct influence on skin penetration. However, their amphiphilic properties allow them to form new systems with the body s constituents and even to change the physical state of water in the skin. By this means, a pathway is cleared for other hydrophilic substances to gain entry into the general circulation. 

Rieger, M.M. and Deems, D.E. (1974). Skin Moisturizers. II. The effects of cosmetic ingredients on human stratum comeum. J. Soc. Cosmet. Chem. 25 253. 

Absorption Across the Skin. An aqueous carrier may be used for a variety of dermal products. In fact, carriers can be designed to limit the transportation of the penetration of the active ingredient (such as an insect repellent), if the desired effect is to keep the activity on the surface of the skin. Once again, however, only those materials that are dissolved will be available for penetration across the skin to gain access to the systemic circulation. For almost all chemicals in or about to enter commerce, dermal penetration is a passive process. The relative thickness of the skin makes absorption (into the systemic circulation) slower than the absorption across the GI or pulmonary barriers. This is compounded by the fact that the stratum comeum ftmction is to be impervious to the environment. One of the skin s major functions is protection from infection. Once a chemical penetrates into the dermis, it may partition into the subcutaneous fat. Essentially, absorption across the skin is a two-step process with the first being penetration and deposition into the skin and the second being release from the skin into the systemic circulation. The pattern of blood levels obtained via dermal penetration is generally one with a delayed... 

Given the overwhelming influence of the physical properties of skin in determining bioavailabilities via the dermal route, assessment of dermal penetration is one area in metabolism and toxicology where in vitro methods can be effectively used to predict in vivo results and to screen chemicals. Apparatus and equipment exist that one can use to maintain sections of skin (obtained from euthanized animals or from human cadavers or surgical discard) for such experiments (Holland et al., 1984). These apparatus are set up to maintain the metabolic integrity of the skin sample between two reservoirs the one on the stratum comeum side, called the application reservoir and the one on the subcutaneous side, called the receptor reservoir. One simply places radiolabeled test material in the application reservoir and collects samples from the receptor fluid at various time points. 

Parameters Controlling Absorption. The absorption of a chemical into the skin is a function of the nature of the molecule, the behavior of the vehicle, and the status of the skin. Three major variables account for differences in the rate of absorption or flux of different topical chemicals or of the same molecule in different vehicles the concentration of the molecule in the vehicle, the partition coefficient of chemical between the stratum comeum and the vehicle, and the diffusion coefficient of molecule in the stratum comeum (Garner and Matthews, 1998). 

Finally, intact stratum comeum is an excellent barrier, but in disease states the resistance to absorption is rapidly lost and absorption can be facilitated. 

Skin tape stripping can be used to determine the concentration of chemical in the stratum comeum at the end of a short application period (30 min) and by linear extrapolation predict the percutaneous absorption of that chemical for longer application periods. The chemical is applied to skin of animals or humans, and after a 30-minute skin contact application time, the stratum comeum is blotted and then removed by successive tape applications. The tape strippings are assayed for chemical content. There is a linear relationship between this stratum comeum reservoir content and percutaneous absorption. The major advantages of this method are (1) the elimination of urinary and fecal excretion to determine absorption and (2) the applicability to nonradiolabeled determination of percutaneous absorption, because the skin strippings contain adequate chemical concentrations for nonlabeled assay methodology. 

Figure 1.2 Cross sections of (A) full-thickness skin, x 100 (B) dermatomed skin, x 100 (C) heat-separated epidermis, x400 and (D) trypsin isolated stratum comeum, x400. (Images courtesy of Leon Muijs, Biopharmaceutics Pharmaceutical Technology, Saarland University, Germany).

Stratum Comeum The cornified skin layers may be isolated by digestion of the connective epidermal tissue using trypsin in buffer solutions of pH 7.4. 

P. W. Wertz and D. T. Downing. Stratum comeum Biological and biochemical considerations. In J. Hadgraft and R. Guy (eds.), Transdermal Drug Delivery, Marcel Dekker, New York, Basel, 1989, pp. 1-22. 

A. P. M. Lavrijsen, J. A. Bouwstra, G. S. Gooris, A. Weerheim, H. E. Bodde, and M. Ponec. Reduced skin barrier function parallels abnormal stratum comeum lipid organization in patients with lamellar ichthyosis. J. Invest. Dermatol. 105 619-624 (1995). 

---